Genome-wide linkage scan for genes influencing plasma triglyceride levels in the Veterans Administration Genetic Epidemiology Study.
OBJECTIVE
Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes.


METHODS
We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis.


RESULTS
After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 +/- 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 x 10(-5)). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES.


CONCLUSIONS
Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.
Coletta
Dawn K
DK
Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. dawn.coletta@asu.edu
Schneider
Jennifer
J
Hu
Shirley L
SL
Dyer
Thomas D
TD
Puppala
Sobha
S
Farook
Vidya S
VS
Arya
Rector
R
Lehman
Donna M
DM
Blangero
John
J
DeFronzo
Ralph A
RA
Duggirala
Ravindranath
R
Jenkinson
Christopher P
CP
D002874:Chromosome Mapping / Q000379:methods; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D017058:Mexican Americans / Q000235:genetics / Q000706:statistics & numerical data; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D013781:Texas / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood*; D014728:Veterans
D014280:Triglycerides